Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health, Farmington, CT, 06030, USA.
Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, UConn Health, Farmington, CT, 06030, USA.
Sci Rep. 2022 Apr 28;12(1):6960. doi: 10.1038/s41598-022-10603-3.
Bone regenerative engineering could replace autografts; however, no synthetic material fulfills all design criteria. Nanocarbons incorporated into three-dimensional printed (3DP) matrices can improve properties, but incorporation is constrained to low wt%. Further, unmodified nanocarbons have limited osteogenic potential. Functionalization to calcium phosphate graphene (CaPG) imparts osteoinductivity and osteoconductivity, but loading into matrices remained limited. This work presents ultra-high content (90%), 3DP-CaPG matrices. 3DP-CaPG matrices are highly porous (95%), moderately stiff (3 MPa), and mechanically robust. In vitro, they are cytocompatible and induce osteogenic differentiation of human mesenchymal stem cells (hMSCs), indicated by alkaline phosphatase, mineralization, and COL1α1 expression. In vivo, bone regeneration was studied using a transgenic fluorescent-reporter mouse non-union calvarial defect model. 3DP-CaPG stimulates cellular ingrowth, retains donor cells, and induces osteogenic differentiation. Histology shows TRAP staining around struts, suggesting potential osteoclast activity. Apparent resorption of 3DP-CaPG was observed and presented no toxicity. 3DP-CaPG represents an advancement towards a synthetic bone regeneration matrix.
骨再生工程可以替代自体移植物；然而，没有任何一种合成材料能满足所有的设计标准。纳米碳被整合到三维打印（3DP）基质中可以改善性能，但整合的含量受到限制。此外，未经修饰的纳米碳的成骨潜力有限。功能化的钙磷石墨烯（CaPG）具有骨诱导性和骨传导性，但负载到基质中的含量仍然有限。本工作提出了超高含量（90%）的 3DP-CaPG 基质。3DP-CaPG 基质具有高孔隙率（95%）、中等硬度（3MPa）和机械强度。体外实验表明，它们具有细胞相容性，并能诱导人骨髓间充质干细胞（hMSCs）的成骨分化，碱性磷酸酶、矿化和 COL1α1 表达表明了这一点。在体内，使用转基因荧光报告鼠非愈合性颅骨缺损模型研究了骨再生。3DP-CaPG 刺激细胞向内生长，保留供体细胞，并诱导成骨分化。组织学显示在支柱周围有 TRAP 染色，表明潜在的破骨细胞活性。明显观察到 3DP-CaPG 的吸收，没有毒性。3DP-CaPG 代表了朝着合成骨再生基质的一个进步。
